5ern

Structural highlights

Function

FC1_PHOAM Multifunctional diterpene synthase; part of the 2 gene clusters that mediate the biosynthesis of fusicoccins, diterpene glucosides that display phytohormone-like activity and function as potent activators of plasma membrane H(+)-ATPases in plants by modifying 14-3-3 proteins and cause the plant disease constriction canker (PubMed:17360612, PubMed:26734760). The first step in the pathway is performed by the fusicoccadiene synthase PaFS that possesses both prenyl transferase and terpene cyclase activity, converting isopentenyl diphosphate and dimethylallyl diphosphate into geranylgeranyl diphosphate (GGDP) and successively converting GGDP into fusicocca-2,10(14)-diene, a precursor for fusicoccin H (PubMed:17360612, PubMed:26734760). Fusicoccadiene synthase is an allosteric enzyme for GGPP cyclization that generates 64% fusicoccadiene, 9% delta-araneosene, and one additional unidentified diterpene product, when incubated with GGPP (PubMed:26734760). In the absence of isopentenyl diphosphate (IPP), PaFS can also solvolyze the shorter chain geranyl diphosphate (GPP) and farnesyl diphosphate (FPP) as alternative substrates to yield predominantly acyclic products. FPP is converted to farnesol (60.5%), nerolidol (14.0%), and farnesene (14.0%), while GPP is converted to a mixture of geraniol (59.5%) and linalool (35.0%) (PubMed:26734760). The second step is the oxidation at the C-8 position by the cytochrome P450 monooxygenase PaP450-2 to yield fusicocca-2,10(14)-diene-8-beta-ol (PubMed:22870285). The cytochrome P450 monooxygenase PaP450-1 then catalyzes the hydroxylation at the C-16 position to produce fusicocca-2,10(14)-diene-8-beta,16-diol (PubMed:22870285). The dioxygenase fc-dox then catalyzes the 16-oxydation of fusicocca-2,10(14)-diene-8-beta,16-diol to yield an aldehyde (8-beta-hydroxyfusicocca-1,10(14)-dien-16-al) (PubMed:21299202, PubMed:22870285). The short-chain dehydrogenase/reductase fc-sdr catalyzes the reduction of the aldehyde to yield fusicocca-1,10(14)-diene-8-beta,16-diol (PubMed:21299202, PubMed:22870285). The next step is the hydroxylation at C-9 performed by the cytochrome P450 monooxagenase PaP450-3 that leads to fusicoccin H aglycon which is glycosylated to fusicoccin H by the O-glycosyltransferase PAGT (PubMed:22870285). Hydroxylation at C-12 by the cytochrome P450 monooxygenase PaP450-4 leads then to the production of fusicoccin Q and is followed by methylation by the O-methyltransferase PAMT to yield fusicoccin P (PubMed:22870285). Fusicoccin P is further converted to fusicoccin J via prenylation by the O-glucose prenyltransferase PaPT (PubMed:22287087). Cytochrome P450 monooxygenase PaP450-5 then performs hydroxylation at C-19 to yield dideacetyl-fusicoccin A which is acetylated to 3'-O-deacetyl-fusicoccin A by the O-acetyltransferase PaAT-2 (PubMed:22870285). Finally, a another acetylation by the O-acetyltransferase PaAT-1 yields fusicoccin A (PubMed:22870285).^{[1] [2] [3] [4] [5]}

References

1. ↑ Toyomasu T, Tsukahara M, Kaneko A, Niida R, Mitsuhashi W, Dairi T, Kato N, Sassa T. Fusicoccins are biosynthesized by an unusual chimera diterpene synthase in fungi. Proc Natl Acad Sci U S A. 2007 Feb 27;104(9):3084-8. doi:, 10.1073/pnas.0608426104. Epub 2007 Feb 20. PMID:17360612 doi:http://dx.doi.org/10.1073/pnas.0608426104
2. ↑ Ono Y, Minami A, Noike M, Higuchi Y, Toyomasu T, Sassa T, Kato N, Dairi T. Dioxygenases, key enzymes to determine the aglycon structures of fusicoccin and brassicicene, diterpene compounds produced by fungi. J Am Chem Soc. 2011 Mar 2;133(8):2548-55. doi: 10.1021/ja107785u. Epub 2011 Feb, 7. PMID:21299202 doi:http://dx.doi.org/10.1021/ja107785u
3. ↑ Noike M, Liu C, Ono Y, Hamano Y, Toyomasu T, Sassa T, Kato N, Dairi T. An enzyme catalyzing O-prenylation of the glucose moiety of fusicoccin A, a diterpene glucoside produced by the fungus Phomopsis amygdali. Chembiochem. 2012 Mar 5;13(4):566-73. doi: 10.1002/cbic.201100725. Epub 2012 Jan , 27. PMID:22287087 doi:http://dx.doi.org/10.1002/cbic.201100725
4. ↑ Noike M, Ono Y, Araki Y, Tanio R, Higuchi Y, Nitta H, Hamano Y, Toyomasu T, Sassa T, Kato N, Dairi T. Molecular breeding of a fungus producing a precursor diterpene suitable for semi-synthesis by dissection of the biosynthetic machinery. PLoS One. 2012;7(8):e42090. doi: 10.1371/journal.pone.0042090. Epub 2012 Aug 1. PMID:22870285 doi:http://dx.doi.org/10.1371/journal.pone.0042090
5. ↑ Chen M, Chou WK, Toyomasu T, Cane DE, Christianson DW. Structure and Function of Fusicoccadiene Synthase, a Hexameric Bifunctional Diterpene Synthase. ACS Chem Biol. 2016 Jan 6. PMID:26734760 doi:http://dx.doi.org/10.1021/acschembio.5b00960